ABSTRACT
Steroid-induced necrosis of the femoral head （SNOFH） is a common orthopedic disease，which is difficult to cure and has poor clinical prognosis. The number of SNOFH patients in China is still increasing year by year，which seriously threatens human health. Long-term non-standard or short-term extensive use of hormone （GC） is an important reason for the occurrence of this disease. At present，SNOFH is mostly treated by surgical methods such as hip replacement，which has limitations of great harm to patients and high cost. In recent years，with the continuous deepening and innovation of traditional Chinese medicine（TCM） research，the use of TCM to treat SNOFH has been widely used in clinical practice. The main TCM pathogenesis of SNOFH is kidney deficiency and blood stasis. Therefore，TCM monomer and compound compound of tonifying kidney and promoting blood circulation are used to treat SNOFH. And TCM has obvious therapeutic effect，small side effects，less cost and other advantages. Glycoprotein/beta chain protein secretion （Wnt/beta- catenin） signaling pathway as a classic signaling pathway is closely related to the bone，between its by promoting bone marrow mesenchymal stem cell update，enhance the activity of osteoblast and suppress the apoptosis，which adjust the metabolic balance of bone tissue，increase bone density，will play an important role in the process of bone formation. In recent years，the use of TCM monomers and compounds to regulate Wnt/β-catenin signaling pathway to accelerate bone marrow mesenchymal stem cells，promote their transformation into osteoblasts，and maintain bone metabolic balance mechanism to treat SNOFH has become a new research hotspot. This article reviews the research progress of TCM in the prevention and treatment of SNOFH by regulating Wnt/β-catenin signaling pathway，in order to provide reference for the application of TCM in the treatment of SNOFH.
ABSTRACT
As a threat to human health， steroid-induced osteonecrosis of femur head is a common refractory orthopedic disease mainly caused by glucocorticoids， with poor prognosis and unclear pathogenesis. Osteogenesis-associated signaling pathways play an important role in bone formation. Glucocorticoid-induced abnormal activation and transport of these signaling pathways lead to abnormal differentiation of bone marrow mesenchymal stem cells， dysfunction of bone metabolism， and osteogenesis disorders， which may be the main reasons for the occurrence and development of steroid-induced osteonecrosis of femur head. Bone formation and remodeling need the participation of bone marrow mesenchymal stem cells， which are stem cells characterized by continuous self-renewal and differentiation. The key to strengthening bone remodeling is to improve the osteogenic differentiation capacity， which is the key point to inhibit bone resorption and prevent bone marrow mesenchymal stem cells from differentiating into osteoclasts. Traditional Chinese medicine （TCM） has been used in the treatment of osteonecrosis in ancient times. It is recorded in the Treasury of Words on Materia Medica （《本草汇编》） that "The deficiency in the lower energizer cannot be tonified without Eucommiae Cortexz.The soreness in lower legs cannot be alleviated without Eucommiae Cortex...The pain in the waist and knee cannot be relieved without Eucommiae Cortex...Tonifying liver and invigorating kidney， Eucommiae Cortex is an essential medicine." This indicates that ancient physicians have already begun to use the liver-tonifying， kidney-invigorating， and sinew-bone-strengthening effects of Eucommiae Cortex for the treatment of osteonecrosis. As the national support for the development of TCM strengthens， increasing studies have been conducted on the TCM prevention and treatment of steroid-induced osteonecrosis of femur head. Studies have suggested that Chinese medicinal herbs can exert a positive effect on the differentiation of bone marrow mesenchymal stem cells by affecting targeted signaling molecules， and promote osteogenesis and bone defect repair， thus combating the occurrence and development of steroid-induced osteonecrosis of femur head. The regulation of osteogenic signaling pathway by Chinese medicines to prevent steroid-induced osteonecrosis of femoral head has become a hot research topic. This article reviews the studies about the prevention and treatment of steroid-induced osteonecrosis of femur head with the active components in Chinese medicinal herbs by regulating osteogenic signaling pathways. We then explore the mechanism of the active components in promoting the differentiation of bone marrow mesenchymal stem cells into osteoblasts and inhibiting their differentiation into osteoclasts to facilitate bone formation， aiming to provide a reference for the further study of treating steroid-induced osteonecrosis of femoral head with Chinese medicinal herbs.
ABSTRACT
Bone marrow mesenchymal stem cells （BMSCs） are derived from stem cells isolated from bone marrow and have the potential for multidirectional differentiation and self-renewal. Under certain conditions， BMSCs can be induced to differentiate into osteoblast （OB）， chondrocyte， adipocyte， fibroblast， etc. BMSCs play an important role in maintaining the stability of bone structure and balancing bone metabolism. Promoting the proliferation of BMSCs and inducing their differentiation into OB of great significance for the clinical prevention and treatment of osteoporosis， bone defects， fracture healing， and other diseases. Because the proliferation and osteogenic differentiation of BMSCs are complex processes controlled by multiple genes and regulated by multiple signal transduction pathways， traditional Chinese medicine （TCM） happens to have the advantages of multi-bioactive component， multi-target， and multi-pathway synergism， which can affect the proliferation and differentiation of BMSCs through multiple channels and induce the proliferation of BMSCs. The transcription and expression of genes related to osteogenesis can be enhanced to promote the differentiation of BMSCs into OB， so as to achieve the purpose of preventing and treating osteoporosis， bone defects， and other bone diseases. Based on the literature on the intervention of TCM monomers and compounds in the proliferation and osteogenic differentiation of BMSCs， this study reviewed TCM monomers and compounds in promoting the proliferation and osteogenic differentiation of BMSCs by regulating secreted glycoprotein （Wnt）， neurogenic locus notch homolog protein （Notch）， mitogen-activated protein kinase （MAPK）， phosphatidylinositol-3 kinase （PI3K） /protein kinase B （Akt）， bone morphogenetic protein （BMP）/Smad， Janus kinase （JAK）/signal transducer and activator of transcription protein （STAT）， osteoprotegerin （OPG）/receptor activator of nuclear factor-kappa B （RANK）/RANK ligand （RANKL）， and other signaling pathways to provide new ideas for the research and clinical application of Chinese medicine in the prevention and treatment of orthopedic diseases.